Legal highs present a great threat to health, especially in groups of people experimenting with psychoactive substances. The lack of available knowledge on the biotransformation of these substances necessitates symptomatic treatment in the event of intoxication, which, unfortunately, may be ineffective. Opioids, including heroin analogues, such as U-47700, constitute a special group of designer drugs. In this study, a multi-directional approach to trace the biotransformation of U-47700 in living organisms was used. For this purpose, the in silico assessment (ADMET Predictor) was used first and then followed by an in vitro study using human liver microsomes and the S9 fraction. The biotransformation was then followed in an animal model (Wistar rats). Tissues such as blood, brain and liver were collected for analysis. The study was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The obtained results were compared to those obtained from the analysis of autopsy materials . New psychoactive substances (NSPs) are one of the most serious toxicological threats today, affecting many areas of social life, including legislation, forensics and public health, in addition to being a significant clinical problem . Some suN-[-2-(dimethylamino)-cyclohexyl]-N-methylbenzamide. U-47700 is an alkaline lipophilic compound, very soluble in an acidic environment, and its physicochemical parameters are poorly understood [The compound known as U-47700 was developed in 1970 by Upjohn Company as a potential opioid analgesic, but research on it was abandoned and it was never approved for medical use. The full name of U-47700 according to the IUPAC is 3,4-dichloro-derstood ,6. DurinN-desmethyl-U-47700 (M1), N,N-didesmethyl-U-47700 (M2), hydroxy-N-desmethyl-U-47700 (M3), and hydroxy-N,N-didesmethyl-U-47700 (M4). When comparing the results obtained with urine samples from poisoning victims, all of the metabolites (M1–M4) were observed, although only M1 and M2 were quantified  [N-desmethyl derivatives dominated; thus, at the end of the provided time, the concentration of the N,N-didesmethyl derivative increased [To date, no detailed pharmacokinetic studies have been performed on U-47700, and the only available data come from the analysis of autopsy material and laboratory experiments. Four metabolites were identified in in vitro studies using human liver microsomes: roducts) . Recentlncreased .Opioids were responsible for up to 74% of the fatal poisonings caused by psychoactive substances in 2019, according to the European Monitoring Centre for Drugs and Drug Addiction data. While heroin remains the most widely taken illicit opioid in Europe, and the drug accounts for the majority of drug-related deaths, there is growing concern about the role that other synthetic opioids play in Europe’s drug problem. Although the limited available data indicate that there has been a decline in both fatal and non-fatal fentanyl overdoses in 2020, there are signs that other synthetic opioids (not-fentanyl derivatives) may be playing a more significant role in drug problems in some countries [Observing research directions in NSP forensic toxicology, it covers metabolomic is-sues using in vivo and in vitro models for obtaining data on the safety and pharmacology of these substances, especially soon after their introduction to the drug market. An open question in the area of research concerns the possibility of transferring these to data on a human model and using them for interpretation in death cases for medical–forensic opinion . Tests wOn the basis of the above experiences and observations, it can be seen that the basic reactions occurring during metabolic transformations of U-47700 are demethylation and hydroxylation; however, it is not known yet which cytochrome isoforms are responsible for these transformations, and phase II metabolism has not yet been studied.n = 4 and tested groups: n = 12/6 animals per dose). In the tested groups rats, were randomly placed into a two-dose administration group: 1 and 5 mg/kg. The animals were given a p.o. compound; then, after the appropriate time (30 and 90 min), they were sacrificed. The blood, brain and liver material for the study was collected. Selected tissues were immediately frozen in ice and stored at −20 °C.The experiments were carried out on Wistar rats from the animal housing facility of the Jagiellonian University Medical College in Krakow. A group of 16 male Wistar rats (350–440 g) were kept in a natural day–night cycle at 22 ± 2 °C with food and water available ad libitum. All of the procedures were carried out according to the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Local Ethics Committee (permission number: 306/2019). The animals were divided into two groups (controls—N-desmethyl-U-47700 (purity ≥ 98%), N,N-didesmethyl-U-47700 and U-47700-D6 (CRM) were obtained from Cayman Chemical , and U-47700 (CRP) was obtained from Chiron . Acetonitrile and chloroform were purchased from Merck , while methanol and formic acid were purchased from POCh . All standard stock solutions were pre-pared in methanol (concentration 1 mg/mL) and stored at −20 °C. Further dilutions were prepared using acetonitrile. All chemical solvents and standards were of analytical grade. The 100 mM phosphate buffer (pH 7.4), prepared with ddH2O and 20 mM NADPH (Merck), was solubilized in 100 mM phosphate buffer.The standards of p.o. in two doses: 1 and 5 mg/kg.Drugs: U-47700 (c = 1 mg/mL) dissolved in water and given TM, Thermo Fisher Scientific Inc., NYSE: TMO, Waltham, MA, USA). The HLM was pooled from 50 different individual donors. All of the donors were equally represented for a truer population sample. They were fully characterized for major cytochrome P450 activities and select phase II enzymes. The total protein concentration was 20 mg/mL.The in vitro study consisted of an experiment conducted using a commercially available pool of human liver microsomes (HLM) and S9 (human) enzyme fraction  before use and protected from light.The in silico evaluation included data analysis using the ADMET predictor  software. m/z ratio in the inclusion list) for first-, second-, and third-generation predicted metabolites. This list was incorporated into the data-dependent MS2 (ddMS2) acquisition method operating in positive ESI, but identification of metabolites was not limited to this list. When a mass spectral peak on the inclusion list was detected, an MS/MS spectrum was automatically acquired.Additionally, the in silico prediction software generated a list of accurate mass (expressed as The experiment consisted of incubating U-47700 (c = 150 µg/mL) at different time intervals  according to the protocol recommended by Gibco. The proceedings included the addition of the following to the Eppendorf tubes: 183 µL of 100 mM phosphate buffer, 2 µL U-47700 solution and 5 µL of 20 mg/mL microsomes. The microsomes were pre-incubated with phosphate buffer, and U-47700 in a water bath for 5 min. The reactions were initiated with the addition of 10 µL 20 mM NADPH. Next, the samples were incubated for up to 90 min at 37 °C with gentle agitation. The reaction was terminated by the addition of 200 µL organic solvent—cold acetonitrile. The samples were vortexed and centrifuged at approximately 3000 rpm for five minutes. The supernatant was withdrawn from the protein pellet and analyzed using LC-MS/MS. The results are shown in p.o. through a gastric tube. Two doses (1 and 5 mg/kg b.w.) were used in the study. Animals from the experimental groups were divided into two sub-groups (according to the administered dose); three animals from each subgroup were then decapitated after both 30 min and after 90 min. The control animals received saline. After decapitation, blood and the liver and brain were collected from the animals. The blood was centrifuged and the serum was collected. All of the tissues were preserved until analysis (at a temperature of −20 °C).The next stage of the study was an in vivo study in an animal model. Rats  were used for the study. U-47700 solution in physiological saline was administered D6, concentration 10 μg/mL), 500 μL of water, 250 μL of ammonia water (25%) and 3000 μL of ethyl acetate. The samples were vortexed for 30 s and centrifuged for 10 min at 2000 rpm. The organic phases were collected and dried under a stream of nitrogen at 40 °C. The residue was dissolved in 40 μL of acetonitrile and 10 μL of the reconstituted extract was injected into the LC-ESI-MS/MS system for quantitative analysis.The tissues were homogenized using a sonificator  in water in a proportionate 10 mg of wet tissue to 100 µL of solvent. Next, 500 μL of homogenate were mixed with 10 μL of internal standard , equipped with a degasser, binary pump, autosampler and thermostated column compartment . Chromatographic separation was carried out with a Thermo Scientific BDS HYPERSIL C18 column  and precolumn . The advance column, along with its precolumn was set at 40 °C. The mobile phase was composed of 0.2% formic acid and 2 mM ammonium formate in water (B), and acetonitrile with 0.2% formic acid and 2 mM of ammonium formate (A). Chromatographic separation was achieved using the following gradient program: initially at 10% A for 1.5 min, before being increased linearly to 90% at 2 min, whereupon this was maintained for 2 min and then decreased to 0% at 6 min. Finally, the last 4 min of analysis was kept at 90% B. The flow rate was 0.6 mL/min and the injection volume was 10 µL. A sample volume of 6 μL was injected into the analytical column for compound analysis.m/z were: 329.0/284.0 for U-47700; 314.9/283.9 for N-desmethyl-U-47700; 301.0/172.9 for N,N-didesmethyl-U-47700; and 336.0/286.0 for U-47700-D6 (IS). The total analysis time for a single sample was 12 min. Retention times (RT) for U-47700 and its metabolites were as follows: 8.5 for U-47700 and U-47700-D6; 8.23 for N,N-didesmethyl-U-47700, and 8.3 for N-desmethyl-U-47700. Data acquisition and processing were performed using the Applied Biosystems Analyst version 1.4.2 software.Mass spectrometric analyses were accomplished on an Applied Biosystems MDS Sciex  API 3200 triple quadrupole mass spectrometer equipped with an electrospray ionization (ESI) interface. ESI ionization was performed in the positive ionization mode. High purity nitrogen used as a sheath gas was generated with a nitrogen generator. All of the experiments were carried out in the positive-ion mode. The ion source parameters were as follows: ion spray voltage (IS): 5500 V; nebulizer gas (gas 1): 25 psi; turbo gas (gas 2): 20 psi; temperature of the heated nebulizer (TEM): 350 °C; curtain gas (CUR): 10 psi. The mass spectrometer was operated with a dwell time of 200 ms. To find the optimal parameters of the ion path and ion source of the studied compound, quantitative optimization was carried out through direct infusion of the standards using a Hamilton syringe pump . The multiple reaction monitoring (MRM) mode of the dominant product ion for each compound was realized using optimal conditions. The monitored ions with values N-desmethyl-U-47700 and N,N-didesmethyl-U-47700) in the samples were calculated using the calibration curve that was prepared on the same day and analysed in the same analytical run. Calibration curves were constructed after analysing tissue samples collected from naive rats. The homogenates were spiked with U-47700 and its metabolites at the following concentration: blank, 0.1, 1, 10, 25, 50, 100 ng/mg. U-47700-D6 was used as the IS. These samples were analysed according to the procedure described for sample preparation , in vitro methods were used first. In affinity studies, the Ki values for U-47700 were Ki = 0.91; 110 and 480 nM for μ, κ, and δ receptors, respectively. For the comparison of Ki to morphine, it is 0.213; 27.9; 111 nM for μ, κ, and δ, respectively, whereas in the activity assays, it is 140; 201 and 4540 nM for μ, κ, and δ, respectively . In vitro studies suggest that because U-47700 has a lower affinity for receptors than morphine, it should act less well. The pharmacokinetic profile of the com-pound plays a significant role in U-47700 for µi opioid receptors (in relation to morphine), resulting from other physicochemical parameters. U-47700 is much more lipophilic in relation to morphine ,13,14. UThe problem of substance abuse that affects the central nervous system is still valid despite constantly revised legal regulations. This is due to the fact that ongoing basic re-search yields little knowledge, while experimentation with new psychoactive substances carries a high health risk, especially among young people. Adding to the risk is the fact that many NPS undergo biotransformation in the body to equally active (or often more potent) derivatives. In our work, we undertook a study of the biotransformation of a synthetic opioid—compound U-47700. In the case of this compound, its metabolites were found to have a lower toxic potential and a weaker affinity for opioid receptors .In the first stage, an in silico test was performed with the use of ADMET Predictor software , where proposals for 13 derivative compounds were obtained based on the physicochemical properties of the starting structure. The next step involved in vitro studies using HLM and commercially sourced S9 fractions. In order to complete the research, a simple in vivo experiment was performed on an animal model (rats), which made it possible to confirm certain assumptions and to track the distribution of the studied metabolites in tissues such as blood, brain and liver. The conducted research is a precursor to further analysis, expanded to include all possible metabolites formed in various types of tissue—from blood to nervous tissue. To date, studies on NSOs’ metabolism have been limited due to the variability of NPSs. In addition, where poisoning with this compound is concerned, the first priority is to save the poisoned person before then determining the cause of the poisoning. Confirmation of the presence of the parent substance is sufficient to initiate treatment. However, an equally important aspect is the issue of the metabolites formed, including their pharmacological activity, which contributes to many factors, including the course of poisoning. By analysing the scientific literature describing the metabolism of the opioid U-47700, one can notice the growing interest in the biotransformation of this compound. Undoubtedly, an important element of such research is the possibility of using currently available research tools, such as in silico analysis and in vitro tests. These are tools that allow you to conduct research in accordance with the 3Rs  rules and provide a lot of valuable information allowing for a more complete interpretation of the results from poisoning cases ,16.N-desmethyl-M1 and hydroxylation of M1 to hydroxy-M1 are residual processes, with the probability of the formation of metabolites at 1% and 5%, respectively. Similarly, the processes of hydroxylation of the U-47700 aromatic ring, leading to hydroxy-U-47700, and hydroxylation of the alkyl group, leading to hydroxy-U-47700′, are residual processes, with the probability of metabolites’ formation at 3%. One of the many features of the ADMET Predictor is the ability to predict biotransformation pathways of a given substance along with the determination of specific isoenzymes responsible for particular transformations  of the parent compound . The prormations . Informarmations . In the rmations . The anaIn vivo studies using HLM fractions showed a rapid depletion of the parent substance—U-47700 for 15 min. At the same time, a build-up of M1 and M2 metabolites was observed, with M2 continuing its rapid growth for 90 min, and M1 declining slightly for 15 min to the 90 min time point A. In theN-desmethyl derivative U-47700 was mainly observed in the examined tissues (liver and brain) after 90 min. The profile of the formed metabolites was similar to that in the case of the higher dose—5 mg/kg b.w. as shown in N-desmethyl-U-47700 after both 30 min and 90 min. In animals dosed with 5 mg/kg b.w., U-47700 appears to be biotransformed more slowly, especially in the liver, but the N,N-didesmethyl derivative pathway predominates. A p.o. dose of 5 mg/kg b.w., in our opinion, could be considered subliminally toxic to rats, as the development of cataplexy symptoms was observed until the 90 min time point. Exceeding this dose could result in death through a mechanism of respiratory depression before the end of the experiment. Nordmeier et al. (2021) have shown that the major metabolites of U-47700 have significantly lower biological potential than the parent compound. Therefore, it can be assumed that the pathway involving the formation of N,N-didesmethyl-U-47700 leads to a reduction in the toxicity of the compound [The results obtained from the experiment in the animal model show a difference in the biotransformation pathways of U-47700. When using a lower dose of the compound (1 mg/kg b.w.) in animals, the formation of the compound .Due to the absence of controlled clinical studies of U-47700, in vitro and in vivo  studies can be used to fill an important void in the available data, which can be used for clinical and forensic purposes. The obtained metabolic profile of U-47700 in the tested in vitro and in vivo models is basically consistent with the metabolic profile in terms of quality (M1–M4 metabolites) obtained in the studies of biological material  from patients hospitalized due to poisoning or autopsy material  from others who have died from an opioid overdose ,21.Quantitative studies of the metabolic profile of U-47700 in the animal model for doses of 1 and 5 mg/kg b.w., for the two time points of 30 and 90 min, indicated that the concentrations of U-47700 and its metabolites M1 and M2 were in the ranges of 113–259 ng/mL; 179–625 ng/mL and 132–530 ng/mL, respectively . These rThe in vitro and in vivo study of the metabolic profile of NPS is a useful tool for providing data. This may be useful in terms of diagnosis, assessment of the severity of poisoning and treatment for the purposes of clinical toxicology, or the toxicological distinction of “rapid deaths” and “delayed deaths” ,25, pred


High-molybdenum-vanadium high-speed steel is a new type of high-hardenability tool steel with excellent wear resistance, castability, and high-temperature red hardness. This paper proposes a composition design of high-molybdenum-vanadium high-speed steel for rolls, and its specific chemical composition is as follows (wt.%): C2%, Mo7.0%, V7.0%, Si0.3%, Mn0.3%, Ni0.4%, Cr3.0%, and the rest of the iron. This design is characterized by the increase in molybdenum and vanadium in high-speed steel to replace traditional high-speed steel rolls with the tungsten element in order to reduce the heavy elements’ tungsten-specific gravity segregation caused by centrifugal casting so that the roll performance is uniform and the stability of use is improved. JMatPro (version 7.0) simulation software is used for the composition design of high-molybdenum-vanadium high-speed steel. The phase composition diagram is analyzed under different temperatures. The content of different phases of the organization in different temperatures is also studied. The martensitic transformation temperature and different tempering temperatures with the different types of compounds and grain sizes are calculated. The process parameters of heat treatment of high-molybdenum-vanadium high-speed steel are optimized. The selection of carbon content and the temperature of M50 are calculated and optimized, and the results show that the range of pouring temperatures, quenching temperatures, annealing temperatures, and tempering temperatures are 1360~1410 °C, 1190~1200 °C, 818~838 °C, and 550~600 °C, respectively. Scanning electron microscope (SEM) analysis of the samples obtained by using the above heat treatment parameters is consistent with the simulation results, which indicates that the simulation has important reference significance for guiding the actual production. Rolling mills perform the continuous plastic deformation of metal on working parts and tools. Various types of alloying elements have been explored and adjusted in rolled materials to meet the production requirements and advance rolling equipment toward large-scale, continuous, automated, high-speed development, as well as to improve the strength of rolled materials and increase their resistance to deformation. With advancements in industrial technology, the demand for steel has increased. Therefore, there is significance in research on improving rolled materials to meet production needs. Research on high-carbon and vanadium high-speed steel has shown  that higIn addition to the development of rolls, China is paying more attention to production. In the 21st century, China’s development of rolls has focused not only on production but also on improving product quality to >95% . HoweverHigh-molybdenum-vanadium high-speed steel belongs to a new type of high-C, high-Mo, high-V, and high-hardenability steel tool with good high-temperature red hardness, casting, molding, and abrasion resistance. However, there are few reports and studies on this steel, with no accurate description of its suitable working environment, chemical composition, or hot working process parameters . In this paper, the simulation can predict and determine the optimum hot working process routes and parameters, as well as provide the theoretical basis for formulating the manufacturing process for mill rolls and roll rings, which is particularly important for selecting the tempering temperature.(1)Determining the organizational composition of high-molybdenum–vanadium high-speed steel cold-rolled rolls and theoretically determining the alloy system by using empirical formulas and discussing the literature.(2)We studied alloy system composition data with JMatPro (version 7.0) materials using simulation software for simulation calculations, including thermodynamic calculations, phase diagram analysis of the alloy composition, thermal property calculations, solidification calculations, hardenability calculations, high-temperature strength calculations, flow stress analysis, and fatigue analysis, to optimize and select the optimal set of material properties for a group of data.(3)Optimizing heat treatment process parameters for roll rings fabricated from high-molybdenum-vanadium high-speed steel, selecting the optimal set of high-speed steel composition data for the phase transition calculation, drawing the Time Temperature Transformation/Continuous Cooling Transformation (TTT/CCT) curve, calculating the martensite transformation temperature, determining the quenching performance, determining energy changes, and developing the optimal heat treatment route.(4)Drawing general conclusions on the virtual manufacturing of high-molybdenum-vanadium high-speed steel mill roll ring materials. We summarized the analysis and discussion to establish the optimum chemical composition and heat treatment process parameters.The subject of our research was high-molybdenum-vanadium high-speed steel. In our study, we investigated the mill roll rings’ working conditions. We selected or designed a suitable composition for high-molybdenum-vanadium high-speed steel mill roll ring materials and determined the most economical and reasonable hot processing route. Our research goals included the following:We relied on the phase calculation platform in JMatPro (version 7.0) simulation software to analyze the solidification process of high-molybdenum-vanadium high-speed steel, the law of phase change, and the optimal casting temperature. We also analyzed the effects of annealing and quenching temperatures on the microstructure and performance to determine the optimal ranges of high-molybdenum–vanadium high-speed steel, casting temperature, and annealing and quenching temperatures. Providing a theoretical basis for selecting the hot processing parameters for these types of materials was also important.The main alloying elements of high-speed steel for mill roll rings are tungsten, molybdenum, vanadium, and chromium, and the total amount of alloy can be as high as 15–20% .W(W) content. It also improves dispersion strengthening and solid solution strengthening. Thus, tungsten can improve the thermal stability of high-speed steel [Ww at 7–8% can satisfy secondary hardness and thermal stability [23C6 carbides is excessive, and that containing M6C carbides is too little. A quenching temperature that is too high will produce very coarse grains and a significant decline in strength and toughness. M6C carbides increase with an increase in W(W), which significantly improves the superheat stability of the steel. However, if W(W) is too high, the roll microstructure in the leucite amount increases, causing carbide particles to be large and unevenly distributed, adversely affecting the thermal fatigue performance of the roll. The roles of molybdenum and tungsten are similar. Molybdenum also forms M6C carbides, with the same tungsten-containing high-speed steel in M6C carbides compared to its lattice. Furthermore, the lattice parameters are almost the same, that is, the density is lower than tungsten, which eliminates the phenomenon of segregation to some extent. Molybdenum in high-speed steel rolls can improve the inhomogeneity of primary carbides and reduce brittleness. Tempering molybdenum’s solid solution can prevent carbide precipitation along the grain boundaries and improve strength and toughness. Therefore, we aimed to replace the tungsten element in traditional high-speed steel rolls by increasing the content of several molybdenum elements in high-speed steel. We also sought to reduce tungsten in centrifugal casting caused by segregation to make the radial properties of the rolls uniform and improve the rolls’ stability.In high-speed steel tungsten, molybdenum’s chemical properties are similar to carbide-forming elements and its role is nearly the same. It can improve red hardness, and its impact on the organization of high-speed steel transformation and performance is nearly the same. The main difference lies in the molybdenum created during transformation at lower temperatures . Tungsteed steel . The inftability , but theW(W) = 0%, and molybdenum content W(Mo) = 7.0%. At this time, the tungsten equivalent of W(Weq) =W(W) + 2W(Mo) = 14% < 15%, thus ensuring that the high-speed steel has good wear resistance and toughness.Considering the comprehensive analysis above, our study is characterized by high-molybdenum high-speed steel with no added tungsten elements: tungsten content W(V) in high-speed steel is equivalent to shifting all the points in the solidification phase diagram to the left. As the amount of W(V) increases, the eutectic reaction temperature of high-speed steel decreases [2C carbides and inhibits skeletal M6C carbides. MC carbides have the highest hardness and high-temperature austenitization in various high-speed steel carbides. When MC carbide dissolution is difficult, it exists in the remaining phase, which is conducive to grain refinement and improves wear resistance. After the amount of W(V) in high-speed steel rolls exceeds 8% [3C carbides appear in the eutectic organization, reducing the wear resistance of high-speed steel rolls. In addition to purifying steel, vanadium in high-speed steel rolls reduces inclusions and gas content and improves high-speed steel rolls’ resistance to thermal shock [W(V) in high-speed steel rolls is kept between 3.0 and 8.0%. Thus, the vanadium content of high-speed steel designed in this study was W(V) = 7.0%.Vanadium has a strong affinity for carbon; thus, increasing the amount of ecreases , and theceeds 8% , low-haral shock . Therefo7C3 carbides, which improves the wear, heat, and oxidation corrosion resistance of the matrix. Chromium promotes the precipitation of fine M23C6 carbides in the matrix [6C carbides of high-speed steel, which can also form M23C6 carbides. M23C6 carbides can be completely dissolved at lower quenching temperatures, allowing the solid solution to reach carbon–chromium saturation without affecting grain size. Chromium can also promote austenite in completely dissolved M6C carbides, thereby improving the hardenability and red hardness of high-speed steel. In high-speed steel tempered at 450–525 °C, part of the chromium precipitation from the martensite promotes diffuse hardening. The other part of the chromium retained in the α-solid solution prevents softening when heated to higher temperatures. The addition of W(Cr) 3–4% can obtain slightly higher secondary hardness. Chromium in high-speed steel can also reduce oxidation. When the W(Cr) amount is too high, excess chromium is involved in tempering carbide precipitation. Chromium-containing carbides are easy to precipitate at lower temperatures, reducing the thermal stability of high-speed steel. It has been found [7C3 carbides and decreases the number of MC carbides in high-speed steel rolls, which is detrimental to wear resistance. Rolls with low W(Cr) can develop rough surfaces due to preferential abrasion of the substrate and the rolled materials’ adherence to the roll surface, increasing the friction coefficient between the rolls and the rolling force. Roll surface roughness can be improved by increasing the amount of W(Cr) and reducing the rolling force so that the roll contains a certain amount of M7C3 carbides. W(Cr) is also conducive to improving the thermal shock resistance of the high-speed roll. Therefore, the appropriate W(Cr) content in high-speed steel rolls is between 3.0 and 7.0%. Accordingly, the chromium content of high-speed steel designed in this study was W(Cr) = 3.0%.Chromium plays a significant role in preventing oxidation and preventing carbon from forming Me matrix , which ce matrix  studied We added small amounts of other elements to high-speed steel, such as silicon, manganese, nickel, etc., to improve its performance.2C in the re-heating decomposition of M6C and MC carbides, which eliminates columnar M2C carbides [Silicon is a non-carbide-forming element. It can promote the formation of high-speed steel solidification in conventional high-speed steel by reducing harmful Mcarbides  to refincarbides . The sil1 temperature to decrease in high-speed steel. An increase in W(Mn) reduces the thermal stability and secondary hardness of high-speed steel. W(Mn) amounts in ordinary high-speed steel are generally controlled at ≤0.4% [W(Mn) also increases high-speed steel rolls’ brittleness and quenching cracking risk. Mn also causes high-speed steel austenite grain growth. The W(Mn) amount in high-speed steel rolls must be maintained at ≤1.0% to facilitate dosage and production. In our study, the manganese content of high-speed steel W(Mn) was 0.3%.Manganese (Mn) is an element that causes the phase transition point of Aat ≤0.4% . An incrc1 temperature. Kim et al. [W(Ni) content should be maintained at between 0.3 and 1.5%. The nickel content of high-speed steel in this study was W(Ni) = 0.3%.Ordinary high-speed steel does not contain added nickel because it will increase the amount of residual austenite. However, the addition of nickel is also known to improve the mechanical properties of high-speed steel, especially its toughness and plasticity, by reducing the thermal conductivity of high-speed steel and the Am et al.  found thm et al. , affecti2C, M3C, M6C, M23C6 carbides, and other carbide types with all of the strong carbon compounds of high-speed steel. It can also improve the performance of high-speed steel after forging, heat treatment, and other processes [Carbon is the most important constituent element in high-speed steel, which significantly influences every aspect of high-speed steel manufacturing. Its mechanism of action involves the formation, transformation, dissolution, precipitation, and aggregation of carbides ,30. It crocesses .W(C) amounts based on research proposing the concept of “equilibrium carbon” and determined the amount of high-speed steel W(C) using an empirical formula. Although the formula has been verified in several conventional high-speed steel compositions, it is not universal. In recent years, Duan et al. [W(C) for a multivariate white cast iron similar to a high-carbon high-speed steel roll:The general carbon content of high-speed steel rolls should be between 1.8 and 2.8%. Quenched and heated carbon parts are dissolved in austenite to ensure the hardness of martensite. Part of the alloy carbides undergo diffuse precipitation during tempering, resulting in secondary hardening, which prevents grain growth and increases steel hardness, abrasion resistance, and red hardness. The phase transition process cannot be finished if the carbon content is insufficient, and the finished product will not meet the expected results. However, too high of a carbon content will lead to high-speed steel quenching of residual austenites produced by increasing steel performance, reducing the need for multiple tempering treatments. Therefore, the carbon content of high-speed steel should be based on molybdenum, tungsten, vanadium, chromium, and other elements to determine the carbide ratio of the relationship between the steel to meet all the carbide-forming elements. In other words, this achieves the “carbon balance” that produces the maximum secondary hardening effect so that high-speed steel performance can achieve the optimum. As early as 1964, Steven et al.  summarizn et al.  providedCombined with the known elemental content, the carbon content was calculated to be 2.266%. However, relying on the formula alone is not enough. Simulations through JMatPro (version 7.0) software were determined based on the phase transition’s effect on the actual properties. The equilibrium carbon difference was set at 0.5, with 0.1 as the data interval, according to the known elemental content, using JMatPro’s simulation calculation test. According to the literature ,34,35, tIn summary, according to According to the analog data in 6C, M23C6, and M carbides. The alloy is liquified at temperatures of >1310.42 °C, implying that the melting point of the alloy is 1310.42 °C, and the phase diagram shows the liquid-phase region. When the temperature is lowered, the M carbides begin to precipitate slowly at 1305.04 °C because they mainly comprise VC carbides, which have high hardness and a high melting point. As the temperature decreases, the liquid-phase region of M carbides gradually increases. When austenite appears, the alloy phase area from the liquid phase transforms into the austenite phase area. As the temperature decreases, austenite continues to increase alongside M carbides. When the temperature is reduced to 1258.8 °C, the austenite content reaches a peak, implying that the liquid phase has completely transformed into the austenite phase. As the temperature decreases, the austenite content shows a slight downward trend, whereas M carbides show a slightly higher trend. When the temperature drops to 1250.64 °C, the austenite phase begins to gradually precipitate into M6C carbides. As the temperature continues to fall, M6C carbides increase. When the temperature continues to drop to 852.06 °C, the austenite phase area begins to precipitate ferrite, which marks the beginning of the transition from the austenite to the ferrite phase. As the temperature continues to decrease, austenite gradually dissolves into ferrite, and the ferrite content rises sharply. When the temperature is reduced to 797.78 °C, austenite is completely transformed into the ferrite phase. At this time, the ferrite phase begins to gradually precipitate into M23C6 carbides. As the temperature drops again, four values tend to stabilize: The ferrite phase in the ferrite content, M carbides content in the ferrite phase, M carbides content, M6C carbides content, and M23C6 carbides content.The alloy consists of three phase zones and three carbides, namely, the liquid phase zone, austenite, and ferrite phase zones, and MIn 6C, and M23C6 carbides in this phase.Ferrite is a phase region that alloy steel must pass through during the heating process. 23C6-type carbides according to temperature change. This carbide type mainly consists of iron, chromium, and molybdenum elements. Chromium slowly decreases to between 600 and 800 °C, whereas iron increases. Molybdenum shows a slowly decreasing trend at approximately 18%. Carbon, vanadium, manganese, and nickel element contents are <5%, with no obvious change.23C6 carbides mainly exist in the ferrite phase area at approximately 800 °C during the transformation of ferrite to austenite. Part of the M23C6 carbides and a small portion of ferrite occur in the encapsulation reaction generated by M6C compounds. The remaining M23C6 carbides in the quenching and heating process are dissolved in the austenite. M23C6 carbides in the matrix are granular, with a lower melting point of only approximately 840 °C. Its main role is to promote the secondary hardening effect in the tempering process.According to the high-molybdenum–vanadium high-speed steel phase diagram, M6C carbides are mainly molybdenum carbides for elemental contents present in the temperature change curve. M6C carbides with respect to the molybdenum content have a decreasing trend during the ferrite phase’s transformation to the austenite phase at approximately 800 °C. Molybdenum content appears to have a short period of stabilization when the ferrite phase completely transforms to the austenite phase and continues to show a decreasing trend. The chromium content in M6C carbides is relatively low. The chromium content increases slowly from 4.86% to a peak of 5.89% when the temperature increases from 600 to 806.55 °C, and then decreases to 3.04% when the temperature increases to 1050 °C. The chromium content remains at 3% during the transformation process. The carbon content remains at the 3% level, combining with molybdenum and chromium to form M6C carbides. The vanadium content shows a rising trend throughout the process, and the growth rate reaches its maximum at the node of transformation from the ferrite to the austenite phase. The vanadium content in M6C carbides continues to increase with temperature and finally stabilizes at approximately 4.58%. The nickel and silicon content in M6C carbides is insignificant for this carbide type, remaining almost unchanged from 600 to 1050 °C. M6C carbides are also characterized by a high degree of austenitization, and the vanadium content in M6C carbides remains almost unchanged.Molybdenum is also present in large quantities of M carbides. The molybdenum content increases slowly in the ferrite phase, decreases slowly as the ferrite dissolves into austenite, and then decreases sharply when the austenite phase changes into a liquid phase.In addition to molybdenum and vanadium, a small amount of chromium is also present in MC carbides. High-molybdenum-vanadium high-speed steel belongs to over-eutectic steel, which is characterized by high carbon and alloys. This process forms carbides with alloying elements through a sufficient amount of carbon dissolved into austenite to obtain hardness and wear-resistant martensite after quenching. The austenite content directly determines martensite content after heat treatment. Therefore, quenching temperatures should be chosen based on high austenite content. As shown in 6C carbides.As shown in To avoid solidification in the casting process, the casting temperature of the material is generally set above the liquid phase line at 50 °C to 100 °C. Therefore, the casting temperature of the material ranges from 1360 to 1410 °C.c1 or Ac3 above a certain temperature for a certain period of time to austenitize the material. This process is performed after the cooling rate exceeds the critical cooling rate for martensite transformation, improving the steel hardness of the heat treatment method. According to c1 = 797.78 °C and Ac3 = 852.06 °C belongs to eutectic steel. Therefore, the quenching temperature should be greater than the Ac3 temperature value.Quenching is when the steel is heated to AAustenite carbon content is also an important criterion for determining quenching temperatures. As shown in The CCT curve was calculated using JMatPro for TTT/CCT diagrams ranging from 1160 to 1260 °C. The final quenching temperature was determined by the temperature at which 90% of the martensitic transformation occurred. The last column of c1 above 20–40 °C. The annealing temperature will be between 817.78 and 837.78 °C since Ac1 = 797.78 °C.Annealing eliminates the material’s residual internal stresses, prevents material deformation, improves cutting performance, and adjusts the hardness of the material. The process involves heating the steel to a certain temperature, maintaining it for a certain period of time, and then cooling it slowly with the heating furnace. Since high-molybdenum–vanadium high-speed steel belongs to eutectic steel, a spheroidal annealing process must be used to heat the steel to Ac1 below a certain temperature. If 30 °C is the gradient, the tempering temperatures would be 770 °C, 740 °C, 710 °C, 680 °C, 650 °C, 620 °C, 590 °C, and 560 °C. The quenching temperature should be 1200 °C. Tempering is an important process after quenching. Its purpose is to eliminate residual stress after quenching and eliminate residual austenite. Tempering at different temperatures can be obtained from different organizations and by adjusting the performance of steel. For high-molybdenum–vanadium high-speed steel to undergo high-temperature tempering, tempering temperatures should have A3C-type content is significantly reduced when the temperature reaches 680 °C, reducing the material’s tempering stability. Other carbide types show an upward trend, increasing the hardness of the material. In summary, high-molybdenum–vanadium high-speed steel tempering temperatures should be set between 550 and 600 °C.6C compounds and several small granular VCs are distributed on the matrix of tempered martensite, and the austenite grains can be further refined during the quenching process. After 560 °C tempering twice and 570 °C tempering, most of the residual austenite is converted to tempered martensite, and the properties of the steel are further improved.The high-molybdenum-vanadium high-speed steel roll was designed using JMatPro (version 7.0) software for simulation and analysis, the high molybdenum-vanadium high-speed steel meeting the requirements of various components was prepared for smelting, the heat treatment process parameters studied above were applied to the heat treatment at 1170 °C and 1190 °C, respectively, and then the microstructure analysis was carried out. The results are shown in 6C compound has a finer network structure, and the VC grain distribution is more uniform. It can be concluded that using JMatPro (version 7.0) software to design ingredient formulas has important reference significance for guiding practical production.(1)High-alloying elements in high-speed steel carbide types with several different carbides or elements produce different performance characteristics in high-speed steel. The design needs to strictly refer to empirical data.(2)The peak austenite content increases and then decreases as the carbon content increases. However, the carbon content in the austenite increases as the overall carbon content increases. Therefore, the carbon content is determined primarily by its effect on the austenite and martensite transition temperatures.(3)The difference between the carbon content obtained by software simulation and empirical formulas is because the empirical formula does not consider uncontrollable factors such as humidity and temperature in the actual production process. The error is within the controllable range; however, in the actual production process, actual environmental factors should be considered in addition to theoretical calculations.(4)Regarding high-molybdenum-vanadium high-speed steel-cast state organization by the martensitic matrix, M carbides are more important than residual austenite and various types of carbides. Below 1250 °C, the vanadium carbide content is almost unchanged. Granular vanadium was distributed in a fine dispersion. After tempering, the dispersion treatment was even greater, resulting in secondary hardening that can greatly improve the strength, hardness, and abrasion resistance of high-speed steel.(5)We simulated high-molybdenum-vanadium high-speed steel-roll casting temperatures of 1360–1410 °C, quenching temperatures of 1190–1200 °C, annealing temperatures of 818–838 °C, and tempering temperatures of 550–600 °C. The heat treatment of the matrix after distributing a large number of small carbides significantly improved wear resistance to meet usage requirements.We used JMatPro’s material simulation calculations to calculate high-molybdenum-vanadium high-speed steel roll manufacturing and heat treatment process parameters according to the phase diagram method. The following conclusions were drawn:


The General Self-Efficacy (GSE) scale is a validated self-rated questionnaire increasingly used in mental health research. However, despite several psychometric advantages of the GSE scale, its validity in those diagnosed with attention-deficit/hyperactivity disorder (ADHD) has not yet been examined. Moreover, a shorter version of the GSE scale would contribute to a more rational use of resources in extensive multivariate studies. Therefore, as self-rated scales to measure self-efficacy in this population are lacking, the current study aims to develop a condensed version of the GSE for adults with ADHD.a priori formulated hypotheses.A group of patient collaborators (user representatives) from an ADHD organization and health professionals shortened the original 10-item GSE scale to six items and evaluated the content validity of the revised scale. Second, 525 potential participants were invited to participate in a cross-sectional study conducted in 2021 (between January 19th and February 7th). Of them, 403 filled out the GSE-6 for ADHD and two scales measuring psychological well-being and mental health . The psychometric properties of the new scale were examined, testing sr = 0.578) and a moderate negative correlation with the depression and anxiety rating scale PHQ-4 (sr = −0.595).The brief GSE-6 for ADHD displayed good internal consistency with a Cronbach’s α of 0.907. No floor or ceiling effect was detected. Exploratory and confirmatory factor analyses supported a one-factor structure. The GSE-6 also showed a moderate positive correlation with the WHO-5 (The 6-item GSE for ADHD was evaluated to have good content validity. The scale demonstrated good psychometric properties. The results indicate that the GSE-6 may help assess self-efficacy in adults with ADHD. In addiSelf-efficacy is understood as a person’s belief in the ability to control the complex demands of the environment through adaptive actions . Self-efFor adults with ADHD, higher self-efficacy is also associated with lower parenting stress . Self-efSelf-report questionnaires with good psychometric abilities are needed to measure self-efficacy. According to Mokkink et al. , psychomThe GSE-10 has been used to measure self-efficacy in mental health settings , 25 and r = 0.50 and 0.60 after 12 and 28 months, respectively), a positive correlation of the scale with social support and mental health, and a negative correlation with symptoms of depression and anxiety. Bonsaksen et al.  and user representatives from Norwegian ADHD organization – Vårres Regional User-led Center Mid-Norway. The reduction of items was based on consensus reached through group discussions by the health professionals and the user representatives . The rol2.1.2.In the second phase, adults diagnosed with ADHD evaluated the experience of answering the GSE-6 by completing the QQ-10. In this phase, 18 adults from the Norwegian ADHD user-led organization were invited to participate, and 16 participants completed the questionnaires.2.1.3.The 16 recruited adults completed a paper version of the GSE-6 scale and QQ-10. On average, the testing group took 1 to 2 min to complete the GSE-6 scale. Data collection did not include names or other direct identifiers to ensure anonymity and confidentiality. Data were stored as an anonymous SPSS file. The SPSS file was accessible to authorized researchers and was protected with a two-factor authentication login system.2.1.4.The QQ-10 is a10-item questionnaire designed to assess the opinion of patients about their experience using questionnaires during medical care. It includes a five-point Likert scale relating to the subject’s agreement with statements about their experience using the questionnaire . In the 2.1.5.SD), and percentage.The SPSS  was used for statistical analysis. Mplus version 8.8  was used2.2.sr between GSE-6, the five-item well-being scale (WHO-5), and the four-item Patient Health Questionnaire (PHQ-4). Moreover, we assessed structural validity using EFA and CFA. The procedure for validating the GSE-6 for ADHD was based on an earlier validation study of the WHO-5  ;Factor structure: We expected the GSE-6 to have a one factor structure ;sr) with the WHO-5 scale  with the PHQ-4 scale . On the first page, participants read an online consent form, providing information about data storage policies and outlining the study purpose, survey length, and data use. By clicking “I agree,” the participants confirmed that they had read the information about the validation study and that they agreed to participate. A total of 403 adults consented to participate, and data from these were used in further analyses.Several precautions were taken to ensure anonymity and confidentiality. No identification list was created, and data collection did not include names, IP addresses, or other direct identifiers. In addition, to avoid multiple responses from the same individual, the survey settings were set to refuse responses from the same IP addresses. Data were stored as an anonymous SPSS file. The SPSS file was protected with a two-factor authentication login system.2.2.3.The self-rated survey took 15 min to complete using Questback software. Data were collected from January 19 to February 7, 2021.2.2.4.Participants reported demographic data, including gender, educational level, age, marital and work status.2.2.4.1.The GSE-6 items for ADHD (Section 3.1 provides an overview of the items) were ranked in the same way as the GSE-10 using a four-point scale from 1  to 4 (“exactly true”). The total score ranged from six to 24, where the minimum score equals the lowest level of general self-efficacy, and the higher score equals the highest level.2.2.4.2.The WHO-5 is a reliable self-assessment tool comprising five items that evaluate different dimensions of well-being. Participants respond to statements such as “I have felt cheerful and in good spirits,” “I have felt calm and relaxed,” and “I have felt active and vigorous” using a scale ranging from 0 (indicating “at no time”) to 5  . The scaWell-being encompasses a spectrum of emotional aspects that can significantly impact an individual’s self-efficacy beliefs. Recent studies have highlighted a notable link between self-efficacy and subjective well-being , 41, 43.2.2.4.3.PHQ-4  is an ulBoth self-efficacy and anxiety are rooted in an individual’s beliefs regarding their health and capabilities. Research has indicated a relationship between self-efficacy and mental health issues , 42, 47.2.2.5.Data cleaning and initial statistical analysis for Study 2 were conducted using SPSS . The data contained no missing values. Descriptive statistics include the mean, frequency, SD, and percentages. We also calculated floor or ceiling effects, and this was implied if more than 15% of participants obtained the highest or lowest score, respectively . Spearmap < 0.05), a Kaiser–Meyer–Olkin ≥ 0.6, and normally distributed data without outliers  with Oblique Geomin rotation was conducted to assess the factor structure of the GSE-6. Criteria for conducting the EFA were: a sufficiently large sample size, which includes at least 400 participants for conducting EFA , 51, a coutliers .Given the six-items, and that it is recommended that factors have three indicators each , the EFA3.3.1.3.1.1.The following items from the GSE-10 were retained in the revised GSE-6 for adults:Item 1: “I am confident that I could deal efficiently with unexpected events” (GSE-10 Item 4).Item 2: “Thanks to my resourcefulness, I know how to handle unforeseen situations” (GSE-10 Item 5).Item 3: “I can solve most problems if I invest the necessary effort” (GSE-10 Item 6).Item 4: “I can remain calm when facing difficulties because I can rely on my coping abilities” (GSE-10 Item 7).Item 5: “When I am confronted with a problem, I can usually find several solutions” (GSE-10 Item 8).Item 6: “I can usually handle whatever comes my way” (GSE-10 Item 10).3.1.2.SD = 18.3) for the “positive value” domain, and 18% (SD = 13.8) for the domain “negative burden.” The mean for each individual item assessing positive value was more than 2 , that is, the participants primarily answered, “Mostly agree” and “Strongly agree” to questions from the value domain. For the negative burden domain, the mean was less than or equal to 2 (0.63 to 2.00), which means that the participants primarily chose the response options “Mostly disagree” and “Strongly disagree” when answering the burden domain questions. In the second burden domain, the only item that received a mean of 2.00 was Item 8, reflecting that the questions in the GSE-6 for ADHD were “too simple” for participants. The distribution of QQ-10 responses for the positive value domain and the negative burden domain is presented in The QQ-10 results for the GSE-6 for ADHD scale revealed that the mean was 77% (3.2.The results of the hypothesis testing are presented in 3.2.1.SD = 3.807). The distribution of total score for the GSE-6 for ADHD for the sample was normal and is provided in A total of 403 participants (287 women and 109 men) consented to participate and completed the survey. 3.2.2.The EFA supported a one-factor solution by several criteria. One factor had an eigenvalue above 1 (4.624), and inspection of the scree plot and parallel analysis also suggested one factor to be extracted, see The EFA also tested a two-factor solution, which reported item 1 and item 2 to load on factor 1 and the four remaining items to load on factor 2. This model gained following model fit indices: RMSEA = 0.035 [90% CI 0.000–0.089], CFI = 1.000, TLI = 0.999, SRMR = 0.011. However, based on the Kaiser criterion of eigenvalues to exceed 1, inspection of scree plot and parallel analysis, that only two indicators loaded on factor 1, and that the two-factor solution was not considered theoretically meaningful, we decided to retain the one-factor solution.The one-factor solution obtained in the EFA was tested in a CFA in a sample where participants with unknown gender had been removed, to further allow for test of measurement invariance across men and women. The CFA showed acceptable fit indices: RMSEA = 0.097 [0.069–0.127], CFI = 0.995, TLI = 0.992, SRMR = 0.018.In test of measurement invariance, the model was first fitted separate to women and men . Fit ind3.2.3.The GSE-6 for ADHD demonstrated good internal consistency among adults in a Norwegian sample  . In the 3.2.4.sr = 0.578, p < 0.001) and a moderate negative correlation between the GSE-6 and PHQ-4 . Correlation coefficients are presented in SD of the WHO-5 and PHQ-4 are listed in As hypothesized, we found a moderate positive correlation of the GSE-6 and WHO-5 . Another Norwegian study in line with our results was conducted by Leganger et al. (r = −0.21)  . The neg= −0.21) . The ass= −0.21) , where t= −0.21) . HoweverA positive moderate correlation between general self-efficacy and well-being measured with the WHO-5 is consistent with previous studies , 42, 63.Romppel et al.  also valOur findings suggest that the GSE-6 is an easy-to-administer, acceptable, concise, valid, and reliable self-rated tool for measuring self-efficacy among adults with ADHD. As such, the GSE-6 is recommended for use in clinical settings as an assessment tool, aiding mental healthcare professionals, therapists and clinicians in understanding the patient’s self-efficacy in an understudied ADHD adult population. Furthermore, the identified correlations between self-efficacy, well-being and mental health contribute to a more comprehensive understanding of the role of self-efficacy in a clinical setting. These findings can guide clinical practice and future research by contributing to the development of educational interventions and treatment approaches fostering self-efficacy and psychological well-being.4.1.A particular strength of the current study was the participation of patient representatives in adapting the GSE-6 for ADHD. This ensures that the patient perspective related to language perception, accessibility of understanding and relevance of the scale items is preserved. The use of the QQ-10 to evaluate the content validity of the GSE-6 is a strength of the study, nevertheless, for a more accurate assessment of face validity, qualitative interviews should be conducted. In addition, only 16 people completed the QQ-10 questionnaire, which is a limitation. However, even though the sample might not entirely represent the ADHD-population, these participants were patient collaborators and user representatives from a wide geographical area in Mid Norway. Yet, this sample’s size limitation should be considered when designing future GSE-6 validation studies. Further studies with a larger number of participants are required to assess the convenience and ease of use of the GSE-6 for ADHD.In the second phase, participants reported to have been diagnosed with ADHD. However, the ADHD-diagnosis was not confirmed through structured clinical interviews. Therefore, further investigation on the content and construct validity of GSE-6 in a clinical sample of adults with confirmed ADHD is recommended. Due to the cross-sectional design, we could not evaluate the test–retest reliability of the GSE-6 for ADHD, which is a critical psychometric component, and future studies should use a prospective design to evaluate this. Even though we have a sufficiently large sample size for conducting EFA , 51, the5.This study reports the development and assessment of the validity of the GSE-6 for ADHD, which aims to measure the general self-efficacy of those with ADHD. The 6-item GSE was developed in collaboration with user representatives from the Norwegian user-led ADHD organization, and its content validity was assessed in a nonclinical adult ADHD population using the QQ-10 questionnaire, demonstrating a high positive value score and low negative burden score. The GSE-6 for ADHD demonstrated one-factor structure, and moderate correlations with measures of well-being and symptoms of depression and anxiety were found. Taken together, the results support using the GSE-6 for ADHD to measure general self-efficacy in an adult ADHD population. Future studies should evaluate the scale in clinical populations.The dataset analysed during the current study can be made available from the corresponding author on reasonable written request.The studies involving humans were approved by the Regional Committee for Medical and Health Research Ethics in Central Norway (2021/2081643). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.TS: writing – original draft. TS, AH, and HH: conceptualization. HH: data curation. TS and AH: statistical analyses. TS, HP, HH, JV, MLL-C, and AH: writing – review and editing. MLL-C: investigation. HH and MLL-C contributed to conceptualization and data collection. MLL-C and AH: supervision. All authors have read and agreed to the published version of the manuscript.


The results also indicated that several pre-treatment characteristics, including body mass index (BMI), level of eating disorder (ED) symptoms, and MHRQoL are important for identifying whether a treatment is likely to be effective. Future treatment programs should aim to optimise early improvements in BMI, ED symptoms, and MHRQoL.Anorexia nervosa (AN) is a mental health disorder that has serious physical, emotional and social consequences. Whilst cognitive behavioural therapy for AN (CBT-AN) has demonstrated efficacy, there remains a global need to improve AN treatment. Compulsive exercise activity therapy (LEAP) is an active therapy consisting of the addition to CBT-AN of eight specific sessions that focus on exercise and motivation for behavioural change. This paper presents a secondary analysis of 74 female participants in a randomised control trial of LEAP plus CBT-AN versus CBT-AN alone. The main aim of this study was to explore putative predictors and to estimate the magnitude of changes due to LEAP for specific outcome measures. Participants  were assessed at three successive surveys: baseline, end of therapy, and 6 months post-therapy. The overall effect sizes for changes between baseline to end of therapy and baseline to 6-month follow-up assessment showed large effect sizes (Cohen’s  Anorexia nervosa (AN) is a serious mental health disorder characterised by body image concern and the restriction of energy intake relative to requirements, leading to a significantly low body weight . AN may 2), eating disorder (ED) quality of life (QoL), depression, social adjustment, and ED psychopathology. Furthermore, CBT is accepted as a leading therapy by professionals and in clinical guidelines [A small number of studies have been completed to determine a treatment of choice for adults with AN . A recenidelines . Despiteidelines .Compulsive exercise is an important feature of AN and has received little coverage in clinical research . CompulsA CBT for compulsive exercise in EDs, namely compulsive exercise activity therapy (LEAP)—also known as the Loughborough eating disorders activity programme (LEAP)—has been developed in order to improve treatment outcomes by reducing pathological exercise cognition and subsequent compulsive exercise behaviours . LEAP isThe study, “Taking a LEAP Forward in the Treatment of Anorexia Nervosa: A Randomised Trial”  aimed toThis is a secondary detailed analysis of the original data from an RCT of CBT-AN and LEAP that were previously published as a brief paper . The purDiagnostic and Statistical Manual of Mental Disorders Fifth Revision (DSM-5) criteria for anorexia nervosa (AN), have a BMI of 14 to 18.5, and have reported at least one exercise activity during the previous month. Exclusion criteria included a diagnosis of psychosis or bipolar disorder, current substance dependence, medical instability, and high risk of suicide. A total of 574 cases were assessed for eligibility, of which 78 eligible participants  completed self-report assessments at baseline . Baseline participants were assigned randomly using an external computer-generated system and stratification by location, illness subtype, and medication use into two groups—38 in LEAP and 40 in CBT-AN group—to receive therapy. Participants were blind to the treatment group, provided written informed consent, and were debriefed at the end-of-therapy session. The LEAP module utilised CBT techniques to address unhelpful exercise beliefs and behaviours. The CBT-AN group completed 34 individual sessions of manualised CBT for AN over 8–10 months. Manualised CBT-AN is an active therapy aimed at restoring weight and normal eating behaviours by challenging thoughts and beliefs through behaviour change and cognitive restructuring [The current study is part of a 3-site 2-armed parallel RCT that took place in Sydney, Australia; Leicester, United Kingdom (UK); and New York, United States of America (USA) during the period of 2010–2016. The trial was registered with number ACTRN12610000585022. Participants were recruited from ED clinics and community advertising. To be eligible, participants had to be 18 years or older, retrospectively met Baseline participants were re-assessed via self-report questionnaire at the end of therapy and 6 months after the therapy. At the end of the therapy, a total of 50 baseline participants were re-assessed  with a retention rate of 64.1% (50 out of 78), and at 6-month follow-up, 43 participants were assessed , with a retention rate of 55.1% (43 out of 78). It is to be noted that among the 78 baseline participants, only 4 were male (5.1%), and 74 were female (94.9%). The disproportionate number of males may introduce gender bias in the estimated results, and the results may not be generalizable to the overall population level. Considering gender bias in the sample, only 74 female participants  are included in the final analytic sample .Ethics was approved for this study at each site: the Western Sydney University Human Research Ethics Committee; the Institutional Review Board at Columbia University in New York, USA; and the National Health Service Research Ethics Committee in the UK, as part of the Health Research Authority.2) was recorded by objective measurement using calibrated scales and a stadiometer.Socio-demographic data were obtained at baseline, which included questions on age, marital status, highest level of education, and employment status. BMI ; the Eating Disorder Examination–Questionnaire (EDE-Q); ED-health-related quality of life (EDQoL); general physical and mental health with the SF-12 item Health Status Questionnaire; the Compulsive Exercise Test (CET); psychological distress with the Kessler-10 (K-10); and the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ).We applied the same set of mental health measures at all three assessment periods of data collection. Measures used in this paper included body mass index   measuresThe Kessler-10 (K-10) scale is a measure of psychological distress and assesses symptoms of anxiety and depression . The selThe AN stage of change questionnaire (ANSOCQ) measures motivation to change in patients with AN . The selHealth-related quality of life (HRQoL) was assessed with the SF-12 item Health Status Questionnaire v2  and the The EDQoL is an eating-disorder-specific 25-item measure that examines the extent to which the participant views their AN as affecting their quality of life, with higher scores indicating lower HRQoL. The EDQoL has previously been used to assess disease-specific quality of life in patients with eating disorders  and patip-values < 0.05 from the Bonferroni statistical test were adjusted. Based on the two-way comparisons, we computed effect sizes (Cohen’s d) [d of 0.2 denoting a small effect, 0.5 a medium effect, 0.8 and above a large effect [In the first step, we presented descriptive statistics of baseline sociodemographic characteristics  and psychotropic medication for the LEAP and CBT-AN groups. Continuous variables are presented as means and standard deviation (SD), and categorical variables were presented as percentages. In the next step, we presented mean total scores with 95% confidence interval (CIs) for all outcome measures  by LEAP and CBT-AN participants for those who completed assessments at three points of time: baseline , end of therapy , and 6-month follow-up . The overall mean total scores for all outcome measures were compared between LEAP and CBT-AN groups across all three assessment periods. As the outcome measures are continuous, we applied mixed models to examine the adjusted interaction effects for time  and group  effects. The method allows flexibility in modelling covariance structures involving longitudinal and repeated data of a correlated type, considering within-subject, time-dependent correlations. In addition to this multiple group comparison test between “baseline (T0) vs. end of therapy (T1) assessment”; baseline vs. 6-month follow-up (T2) assessment; and T1 vs. T2 were conducted through the statistical technique ANOVA  for repeated measures. The Bonferroni statistical test was applied to examine the pairwise significant differences across time points  for all outcome measures controlling for LEAP and CBT-AN participants. In order to reduce the risk of type-1 error, which may occur in multiple comparison testing for multiple endpoints, the levels of significance i.e., all p = 0.10), EDE-Q global score (p = 0.133), and EDQoL (p = 0.59) do not differ significantly by study site , to obtain stable estimates, this study used combined participants (n = 74) of three trial places as the analytic sample for statistical analysis.Next, we examined the association of main outcome measures  with patient characteristics and all other outcome measures. For categorical variables, the mean total scores are presented by subgroups; and for continuous variables, correlation coefficients are presented. It is to be noted that the study was part of a 3-site, 2-armed parallel randomised control trial that took place in Sydney, Australia (n = 23); Leicester, United Kingdom (n = 38), and New York, United States of America (n = 13). In order to examine the differences of measures by country of trial controlling for two randomisation groups require larger sample size. As the initial analyses shows that the main outcome measures at baseline for BMI  are included in multiple linear regression analysis to further examine the relative contribution of each of these predictive measures adjusting for age and treatment group. Considering the three assessment periods , three multiple regression analyses were carried out for each of the main outcome measures, i.e., a total of 12 multiple regression analysis were performed. We used SPSS 27  to conduSD = 8.7). Almost half (50.0%) of all participants had completed or were participating in university-level education, 41.9% completed up to high-school-level education, and a minority (8.1%) had obtained a trade certificate. More than two thirds (68.9%) of the participants were single, 28.4% were married, and over half (56.6%) were employed. At the baseline survey, 54.1% reported having purging behaviour, and a similar proportion (54.1%) had taken psychotropic medication (SD = 1.1).The sociodemographic and clinical characteristics of study participants at baseline assessment are reported in dication . Particip = 0.028), all other outcome measures  showed no significant differences by group, adjusting for time effects over the three assessment periods. In addition, none of the outcomes showed statistically significant interactions between groups in terms of assessment time.p = 0.020) and CET (p = 0.006) were found to be significantly higher among the CBT-AN group as compared to the LEAP group. At the 6-month follow-up, except for the CET score (p = 0.016), all other measures do not differ significantly between LEAP and CBT-AN participants.The mean outcome measures score for both LEAP and CBT-AN participants at T1 and T2 showed significant reductions as compared to T0 for EDE-Q global score, weight concern, dietary restraint, eating concern, shape concern, EDQoL, and psychological distress and a significant increase in ANSOCQ and psychological distress score  . Irrespep-values) across different time points  through the Bonferroni statistical test controlling for the LEAP and CBT-AN group participants. Each matched sample comprised all participants who completed each outcome measure between the two time points under comparison. The results in p < 0.05). It is to be noted that between T0 and T1 and T0 and T2, based on raw (unadjusted) p-values, 85% of findings were significant at p < 0.01, and after applying corrections of p-values, 81% of findings become significant at p < 0.01. As shown on the table in p < 0.001) but was not found to be statistically significant among LEAP participants. The mean score of exercise beliefs between T0 and T1 for participants of both intervention groups had overall p = 0.001 but for CBT-AN participants was p = 0.03 (adjusted p = 0.09). Furthermore, the mean scores of all the mental health measures significantly differed between T0 and T2 except for exercise beliefs within each intervention group and SF12MCS among LEAP participants, but combined results for participants in both intervention groups reached significance (p = 0.015 for exercise beliefs and p = 0.001 for SF12MCS). Between T1 and T2, there were no significant differences for any of the outcome measures except for dietary restraint among the CBT-AN group . This might be because of shorter follow-up time duration.d) for each outcome measure as an indication of the magnitude for each outcome by LEAP and CBT-AN group participants for baseline (T0) assessment compared to end of therapy (T1), T0 compared to 6-month follow-up (T2), and T1 compared to T2 assessment. The overall effect sizes for baseline to end of therapy; and baseline to 6-month follow-up assessment showed larger effect sizes (Cohen’s d > = 0.80) for EDE-Q global score, EDQoL, SF12MCS, weight concern, dietary restraint, eating concern, ANSOCQ and psychological distress; and medium effect sizes  for shape concern and the CET. The overall effect sizes for all measures between end of therapy to 6-months follow-up was quite small (d < 0.50), this might be because of shorter follow-up time duration. The effect sizes for baseline to end of therapy assessment showed that effect sizes for LEAP were slightly larger than the CBT-AN group for most of the measures, including EDE-Q global score , EDQoL , weight concern , dietary restraint , and eating concern ; marginally larger effect sizes for CBT were observed for ANSOCQ  and psychological distress . There appears to be no effect for LEAP on BMI at the end of therapy, while CBT-AN shows moderate effect size . The effect sizes for main outcomes by patient characteristics revealed that irrespective of patient characteristics larger effect sizes observed between T0 and T2; effect sizes slightly differ by patient characteristics and treatment group and were not found to be statistically significant (nificant . The effnificant . The chanificant .p = 0.004) and those who reported with no psychotropic medication (p = 0.008).Findings presented in p < 0.05), EDQoL , and ANSOCQ . BMI at T2 was found to be significantly associated with T2 EDQoL , dietary restraint , eating concern  and ANSOCQ .The correlation co-efficient between main outcome measures with other outcome measures and participants characteristics are presented in p < 0.05), T0 SF12MCS , EDQoL , CET scores , ANSOCQ , and psychological distress . A similar significant association was observed between T1 EDE-Q global score with other T1 measures and T2 EDE-Q global score with other T2 measures (Results in measures . As expep < 0.05), employment status , psychotropic medication , T0 EDE-Q global score , CET scores , ANSOCQ , and psychological distress . A similar significant association was observed between T1 SF12MCS and participant’s employment status, psychotropic medication, T1 EDE-Q global score, ANSOCQ and psychological distress. T2 SF12MCS was found to be significantly associated with T2 EDE-Q global score and psychological distress (Findings in distress .p < 0.01), CET scores , ANSOCQ , and psychological distress   . A simil < 0.01) .p < 0.01), followed by between ANSOCQ and shape concern , between weight concern and eating concern , and between shape concern and dietary restraint r = 0.66; p < 0.01). A similar correlation was observed at T1 and T2 (The correlation matrix presented in 1 and T2 . All the1 and T2 . The sigp < 0.05) and a lower value of EDQoL  were significantly associated with higher BMI at T1. The overall model for T1 was significant, accounting for 36.8% of the total variance. The regression model for the 6-month follow-up (T2) measures also shows that lower value of EDQoL  was significantly associated with a higher BMI at T2. The overall model for T2 was significant, accounting for 22.9% of the total variance  and a higher value of EDQoL  were significantly associated with higher EDE-Q global score at T0. The overall model at T0 for EDE-Q global score was significant, accounting for 68.6% of the total variance. The regression model for the T1 measures shows that a lower ANSOCQ score  was associated with a higher EDE-Q global score at T1. The overall model was significant, accounting for 66.2% of the total variance. The regression model for the T2 measures also found that a lower ANSOCQ score  and a higher value of EDQoL  were significantly associated with a higher EDE-Q global score at T2. The overall model was significant, accounting for 64.1% of the total variance  were significantly associated with higher SF12MCS values  and a greater value of the EDE-Q global score  were associated with a higher value of EDQoL (p < 0.01) was associated with higher EDQoL values. All three models were significant, with accounting for 59.7% of the total variance at T0; 58.4% at T1; and 71.3% of the total variance at T2.EDQoL: The regression model for the T0, T1, and T2 measures shows that a higher psychological distress score  for EDE-Q global score, EDQoL, SF12MCS, weight concern, dietary restraint, eating concern, AN stage change, and psychological distress; medium effect sizes (Cohen’s d ranges 0.50 to 0.79) for shape concern; and compulsive exercise for changes between baseline to end of therapy and baseline to 6-month follow-up. The effect sizes for all measures between end of therapy and 6-month follow-up were quite small. This may have been due to the short duration of follow-up or that a small subset of participants might have experienced symptomatic worsening post-treatment. Changes between baseline and end of therapy showed that effect sizes for those in the LEAP group were slightly larger than for those in the CBT-AN group for most of the measures, including EDE-Q global score, EDQoL, weight concern, dietary restraint, and eating concern, whilst marginally larger effect sizes for CBT-AN were observed for ANSOCQ and psychological distress. The effect of therapy was observed in both LEAP and CBT-AN groups even before the 10 weeks of therapy; the EDE-Q global score, EDQoL, and SF12MCS showed significant changes between baseline and 10 weeks of therapy.This paper reports in-depth secondary analysis of the first and to date only RCT in adult women to examine the efficacy of LEAP in a direct comparison with a CBT-AN condition through three successive assessments at baseline, end of therapy, and 6-month post-therapy follow-ups respectively. The findings revealed that there were large effect sizes . The differences in their reported levels of education (p = 0.67), employment status (p = 0.55), and psychotropic medication use (p = 0.98) at baseline were not found to be statistically significant between the two groups (p = 0.84), SF12MCS (p = 0.15), EDQoL (p = 0.10), weight concern (p = 0.05), dietary restraint (p = 0.17), eating concern (p = 0.18), compulsive exercise test (p = 0.87), and exercise beliefs questionnaire , all the analyses were carried out on a combined sample which may not be representative of people receiving treatment for anorexia nervosa for each country or other countries. As with RCTs, for which there are strict inclusion criteria, results also may not be generalizable to all who have a need for treatment as this would include people with, e.g., a diagnosis of bipolar disorder or current substance dependence who were excluded from the present RCT. These study features limit the generalizability regarding the findings. Furthermore, the majority of data used for statistical analyses in this study were obtained using self-report measures. It is likely that more accurate clinical data could have been obtained by using semi-structured interviews in which the interviewer can explore symptoms experienced by participants in depth . Anothero groups . A similp = 0.37 . This fiAnother limitation of the present study was that the level of compulsive exercise accepted for inclusion in the study was very broad, as the eligibility criteria included participants who had participated in at least one form of physical activity in the past month. Although this allows results to be generalised to a wider group of individuals with AN who engage in exercise, further investigation is needed to explore the relationship between LEAP, treatment outcomes, and their predictors for people with high levels of compulsive exercise. Furthermore, the follow-up period was only 6-months, which is relatively shorter compared to other RCT studies. Finally, it must be acknowledged that this RCT was not designed specifically for predictor or moderator analysis.Several key strengths separate this study from previous research. This is one of the few RCTs to examine outcome measures in an outpatient adult sample and the first to examine these in a LEAP trial. The RCT followed a strict double-blind protocol. In particular, the participants were not told which treatment group they were in, therapists were trained and conducted both treatments, and adherence to protocols was assessed by reviewing audio recording of treatment sessions. The study was conducted at multiple sites on three different continents, which improves the generalisability of results. As well as this, the study explored a range of robust and well-established outcomes, including both AN-specific and general measures.As this study was exploratory in nature, future studies should extend and replicate the findings. Future studies using larger samples could examine the predictors and other maintaining factors, specifically affect regulation, which may influence treatment outcome, as lower levels of baseline emotional dysregulation have previously predicted weight increase .This study found large effective sizes for CBT-AN (with or without LEAP) from baseline to (a) end of therapy and (b) to 6-month follow-up in improved ED- and MH-related quality of life (MHRQoL), reduced ED symptomatology and psychological distress, and improved participant motivation to change. Medium effect sizes were found for reduced shape concern and compulsive exercise. Several baseline characteristics, including BMI, level of ED symptoms, and MHRQoL, were found to be important predictors in identifying whether a treatment is likely to be effective. Future treatment programs should aim to reduce psychological distress and increase motivation prior to CBT-AN treatment because although it may not predict change in psychopathology at the end of therapy, participants will be in a better place for eventual recovery.


Preoperative imaging of vascular invasion is important for surgical resection of pancreatic ductal adenocarcinoma (PDAC). However, whether MRI and CT share the same evaluation criteria remains unclear. This study aimed to compare the diagnostic accuracy of high-resolution MRI (HR-MRI), conventional MRI (non-HR-MRI) and CT for PDAC vascular invasion.Pathologically proven PDAC with preoperative HR-MRI  and non-HR-MRI  were retrospectively collected. Vascular invasion was confirmed surgically or pathologically. The degree of tumour-vascular contact, vessel narrowing and contour irregularity were reviewed respectively. Diagnostic criteria 1 (C1) was the presence of all three characteristics, and criteria 2 (C2) was the presence of any one of them. The diagnostic efficacies of different examination methods and criteria were evaluated and compared.P = 0.03). C1 was superior to C2 in the venous assessment using HR-MRI  and in the arterial assessment using non-HR-MRI . The combination of C1-assessed HR-MRI and C2-assessed CT was significantly better than that of CT alone .HR-MRI showed satisfactory performance in assessing vascular invasion (AUC: 0.87–0.92), especially better sensitivity (0.79–0.86 vs. 0.40–0.79) than that with non-HR-MRI and CT. HR-MRI was superior to non-HR-MRI. C2 was superior to C1 on CT evaluation (0.85 vs. 0.79, HR-MRI more accurately assessed PDAC vascular invasion than conventional MRI and may contribute to operative decision-making. C1 was more applicable to MRI scans, and C2 to CT scans. The combination of C1-assessed HR-MRI and C2-assessed CT outperformed CT alone and showed the best efficacy in preoperative examination of PDAC.The online version contains supplementary material available at 10.1186/s12885-023-11451-8. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumour with a 7–9% 5-year survival and the seventh highest mortality rate worldwide , 2. At tVascular invasion is of great clinical importance because it is a predictor of the prognosis and survival of patients with PDAC , 6. MorePreoperative non-invasive imaging evaluations, especially Computed tomography (CT), have been widely used in clinical practice because of their convenience and high resolution , 11. CT This study aimed to evaluate the combination of HR-MRI and gadobutrol in the assessment of PDAC vascular invasion, compare its accuracy with that of non-HR-MRI and CT, and clarify the applicable diagnostic criteria for CT and MRI.The study protocol was approved by the Institutional Review Board, and the requirement for informed consent was waived . All procedures were carried out in accordance with the approved guidelines.A flowchart of the data collection and study design is shown in Fig. All patients in the HR-MRI group underwent gadobutrol-enhanced abdominal MRI using a 3.0-T system  with unenhanced imaging  and contrast-enhanced T1-weighted imaging. The non-ionic gadolinium-based contrast medium  at a dose of 0.1 mmol/kg was injected utilizing a power injector at a rate of 1.5 mL/s followed by a 30 mL saline flush. The specific parameters of each sequence are listed in Table For non-HR-MRI, the patients underwent normal gadolinium-enhanced abdominal MRI using 1.5-T system  or 3.0-T systems . Since most of the patients in this group were examined on the MAGNETOM Prisma, the examination parameters of this scanner are listed in Supplementary Table All MR and CT images were retrospectively reviewed by two abdominal radiologists with 6 and 9 years of experience, respectively, who were blinded to the pathological and clinical data of all patients. Conclusive discrepancies were finally discussed and resolved by mutual consensus after joint reassessment of the images. Tumour location was defined as the head/neck and body/tail of the pancreas, according to the spatial relationship between the tumour and the superior mesenteric vein. The tumour size was measured on axial images using the longest cross-sectional dimension. The relationships between the tumour and celiac trunk artery (CA), hepatic artery (HA), superior mesenteric artery (SMA), splenic artery (SpA), portal vein-superior mesenteric vein (PV-SMV), and gastroduodenal artery (GDA) were recorded. The analysis included circumferential tumour contact , vessel narrowing  and contour irregularity . MR evaluation is based on all axial and coronal images. However, the conventional MRI did not have coronal scan images. In conventional MRI group, we obtained the coronal images by MPR based on dynamic volumetric enhanced axial images with a slice thickness of 2 mm. CT evaluation is based on axial and multiplanar reformation images. In MRI, tumour composition is determined by combining T2 signal, enhancement and DWI restriction to determine tumour boundary, while in CT, tumour boundary is mainly determined by density and enhancement difference. Additionally, the variant anatomy of the vessels was identified before confirming the peripancreatic structures.The invasion of each vessel was determined using two criteria. Criteria 1 (C1): (1) circumferential tumour contact > 180°, (2) vessel narrowing, and (3) contour irregularity. Criteria 2 (C2): (1) circumferential tumour contact > 180°, (2) vessel narrowing, or (3) contour irregularities. The accuracies of different criteria and examination methods were compared.The results of tumour-vessel contact explored by the surgeon in the surgical record and the results in the pathology report were considered the gold standard in this study. Other clinical information, including patient demographics and surgical procedures, were also examined. Surgical procedures were classified as pancreatoduodenectomies, partial pancreatectomies , or exploratory laparotomies.SPSS  and R (version 4.2.2) were used for the analysis. Continuous variables were evaluated using the Kolmogorov–Smirnov normality test. Means and standard deviations (SDs) were used to describe the continuous variables. An independent samples t-test was used to analyse continuous variables. Categorical variables were analysed using the χ2 or Fisher’s exact test.The interobserver agreement of tumour-vessel relationship was evaluated by interclass correlation coefficients (ICCs) for all readers and weighted kappa coefficients for different readers. The interobserver agreement was graded as follows: 0–0.20, slight; 0.21–0.40, fair; 0.41–0.60, moderate; 0.61–0.80, substantial; and 0.81–1.00, almost perfect.P < 0.05. False discovery rate (FDR) was used to correct the P value and obtained the Q value(p.adjust).Receiver operating characteristic (ROC) curves were used to evaluate the predictive efficacy of each group and the criteria of sensitivity (Sen), specificity (Spe), and area under the ROC curve (AUC). The Delong test was used to compare the accuracy of the different evaluation methods. All differences were considered statistically significant at A total of 79 patients who underwent HR-MRI (58 with CT) and 77 without (59 with CT) were enrolled in this study. The clinical information of both groups is shown in Table The interobserver ICC ranged from 0.83 to 0.92 when assessing tumour-vessel relationship. The interobserver differences between different groups and vessels is presented in Table All MR and CT methods had good specificity, but their sensitivity varied widely. HR-MRI showed the highest overall AUC value for all vessel assessments under both criteria, whereas non-HR-MRI showed the worst overall AUC value. Non-HR-MRI was less sensitive than CT and HR-MRI for both the C1 and C2 criteria, especially in assessing arterial invasion, with a sensitivity of only 40%.In the assessment of arterial invasion, all methods showed a high specificity of > 97%, which was better than that of the venous assessment. HR-MRI showed the highest sensitivity and specificity for assessing arterial invasion regardless of the C1 or C2 criteria. In the assessment of venous invasion, CT had the best specificity of up to 98% with the C1 criteria, but a lower sensitivity than HR-MRI.Compared with the C1 criteria, the C2 criteria improved the sensitivity of vascular assessment to some extent while compromising the specificity. The C2 criteria was not inferior to C1 in the overall AUC value, except for a decrease in AUC of the evaluation of venous invasion by HR-MRI. In addition, the evaluation criteria had a greater impact on CT than on MR. Further details are displayed in Table P values and Q values of the DeLong test for comparing the performance of different examination modalities or criteria are shown in Table The In the non-HR-MRI group, the C1 criterion was superior to the C2 criterion in assessing arterial invasion. CT was superior to non-HR-MRI in the assessment of venous and arteriovenous invasion according to C2 criteria, but not significant after FDR correction. HR-MRI was superior to non-HR-MRI for all vessels, regardless of the evaluation criteria.P = 0.029). However, the differences were not statistically significant after FDR correction.The C1 and C2 criteria showed no difference on CT evaluation between the HR-MRI and non-HR-MRI groups. After combining the CT data from groups 2 and 4, the C2 criteria were found to be superior to the C1 criteria in the assessment of venous and arteriovenous invasion (0.85 vs. 0.79, After applying different assessment criteria in different examination methods, CT assessment using the C2 criteria was superior to non-HR-MRI using the C1 criteria in the assessment of the venous and arteriovenous veins. The results of CT evaluation using the C2 criteria did not differ significantly from those of HR-MRI evaluation using the C1 criteria. Therefore, the C2 criteria play an important role in the diagnostic efficacy of CT evaluation.To further evaluate the diagnostic efficacy of the combination of HR-MRI and CT, the presence of vascular invasion in the combined model was defined as a positive diagnosis using MR or CT. The C2 criteria were used for CT diagnosis, while both the C1 and C2 criteria were compared for MRI diagnosis. Patients without CT images were excluded when the two datasets were merged. Among the remaining 58 cases, the C1 and C2 criteria showed no difference in the arterial evaluation, whereas C1 showed better performance in the venous evaluation. This combination significantly improved the sensitivity of venous evaluation. A comparison of the combined and single-modality models revealed that although the combined model had higher overall effectiveness values, only the difference in the CT evaluation was significant. The detailed efficacy rates and comparisons are shown in Tables In recent years, HR-MRI has emerged to display the extent and characteristics of tumours, providing additional valuable information and assisting in treatment decisions –27. Our In this study, the specificity of both CT and MRI evaluations was significantly better than their sensitivity, particularly for arterial evaluation. The possible reasons for this are as follows: First, the gold standard for determining vascular invasion is surgical exploration and pathology, with preoperative imaging determining resectable cases. In these cases, most of the evaluated vessels were spatially distant from the tumours and did not invade them. Second, the arterial diameter is smaller than that of the vein, with a more complex surrounding structure, affecting the observation of the vascular wall and the true positive rate. Third, the small sample size cannot be ignored, and a larger sample needs to be included for validation. Cases of arterial invasion are more difficult to treat because resection and reconstruction could be applied for venous invasion, whereas arterial reconstruction is extremely difficult , 29.When comparing the imaging modalities for the evaluation of venous invasion, the specificity of CT was slightly higher than that of MR, whereas the sensitivity of HR-MRI was higher than that of the other methods. This might be because CT has better spatial resolution and insufficient soft tissue resolution, which is advantageous for observing the spatial tumour–vascular relationship. However, when an inflammatory exudate is present around the tumour, it is difficult to distinguish it from tumour infiltration using CT, resulting in an increased false-positive rate on CT evaluation –32. HR-MWhen comparing the diagnostic criteria, the reason for the improved accuracy with C2 was mainly due to the improved sensitivity after broadening the diagnostic criteria for vascular invasion. However, the C2 criteria did not significantly improve the sensitivity of HR-MRI on venous evaluation but markedly reduced the specificity. This indicates that HR-MRI can accurately determine vascular integrity, but the use of tumour–vascular contact to determine vascular invasion can increase the false-positive rate. In particular, in non-HR-MRI, the C1 criterion showed better performance on arterial evaluation with high specificity. Although the C2 criterion slightly improved the AUC values for the overall vascular assessment in both MRI groups, the difference was not significant. In contrast, assessment of the arterial wall by MRI remains slightly limited owing to the slimmer diameters of the arteries than that of the veins. In the combined assessment of HR-MRI and CT, the C2 criteria did not have a significant impact on the overall MRI evaluation but rather reduced the specificity of the venous assessment. Therefore, the C1 criteria is more applicable to MR assessment than the C2 criteria.Furthermore, the C2 criteria had a greater impact on the diagnostic efficacy of CT than that of MRI, especially for venous imaging. The C2 criterion significantly improved the sensitivity of the assessment but had little impact on specificity. This may be because CT has a better advantage in showing the vascular–tumour contact, but it does not directly and accurately show the vascular integrity. On expanding the invasion criteria to consider only tumour–vessel contact, the false-positive rate did not have a significant impact on the efficacy of CT. This indicates that the probability of vascular invasion is extremely high when the tumour encases the vessel by > 180 ° on CT. Therefore, C2 is more applicable than C1 for CT evaluation of vascular invasion.Using CT alone is challenging for the assessment of vascular involvement, particularly after neoadjuvant therapy, owing to the confounding effects of therapy-related changes such as fibrosis and oedema , 34. DesOur study has several limitations. First, owing to the retrospective design of this study, it was difficult to draw broad conclusions regarding this patient population based on our results alone. Only patients with PDAC who were preoperatively judged operable were included in this study. We used surgical exploration and pathology as the gold standards for assessing vascular invasion. Second, the number of cases was limited, particularly because the number of patients with arterial invasion was small. Tumours defined as definitely unresectable on preoperative imaging, but not verified, were not included. Therefore, the relative percentage of patients with equivocal signs of vascular involvement may have increased, and the number of involved vessels may have decreased, lowering the sensitivity of CT and MR for detecting vascular involvement. Third, the combination of HR-MRI and gadobutrol showed better performance than conventional MRI with traditional gadolinium contrast agents. However, the weights of specific factors must be studied further. Finally, this study was conducted at a single academic institution using HR-MRI data obtained from a single MRI scanner. Data from more centres and scanners are required for further research and validation.In conclusion, HR-MRI provides a more accurate assessment of PDAC vascular invasion than conventional MRI. CT and MRI may not share the same evaluation criteria because CT requires a loose standard to achieve accurate diagnosis. Preoperative HR-MRI combined with CT is recommended to obtain accurate vascular invasion assessments and assist in surgical treatment decision making.Below is the link to the electronic supplementary material.Additional File 1: Non-HR-MRI scan sequence and parameters.Additional File 2: Assessment of GDA invasion